Synthesis , Characterisation , Spectral and Microbial Studies of Transition Metal Complexes of the Drug , Secnidazole

5-Chloromethyl-8-quinolinol hydrochloride was condensed with 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ol in presence of potassium carbonate. The resulting 5-((1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2yloxy)methyl)quinolin-8-ol was characterized by elemental analysis and spectral studies. The transition metal chelates of the same were prepared with Cu, Ni, Co, Mn and Zn and characterized by IR and electronic spectral studies and magnetic properties. The antimicrobial activity of ligand and its metal chelates were screened against various gram positive and gram negative organisms. The results show that all these samples are more or less active agents against various organisms.


Synthesis of 5-((1-(2-methyl-5-nitro-1H-imidazol-1-yl) propan-2-yloxy) methyl) quinolin-8-ol (Formation of MIPQ)
In a round bottom flask, to a suspension of 5-chloromethyl-8-quinolinol (CMQ) hydrochloride (23 g, 0.1mol) in dry acetone (100 mL), 1-(H)-Secnidazole (0.1 mol) was added gradually at room temperature.Potassium carbonate (16.8 g) was added in the mixture and the mixture was refluxed on water bath for 8 h.The resulting solid mass was added in to water and the precipitation was filtered off, washed with boiling water and the air dried.It was dark green amorphous powder.It was insoluble in common organic solvent but soluble only in formic acid and DMSO.

Analysis
The prepared ligand was analyzed for elemental analysis, 1

Synthesis of MIPQ
MIPQ (0.05 mol) was taken in 500 mL beaker.Formic acid was added up to slurry formation.To this slurry water was added till the complete dissolution of MIPQ.It was diluted to 100 mL.In a solution of metal acetate (0.005 mol) in acetone: water (50:50 v/v) mixture (40 mL) 20 mL of above mentioned MIPQ solution (i.e. containing 0.01 M Secnidazole) was added with vigorous stirring at room temperature.The appropriate pH was adjusted by addition of sodium acetate for complete precipitation of metal chelate.The precipitates were digested on a boiling water bath.The precipitates of chelate were filtered off, washed by water and air dried.

Measurements
The elemental contents of C, H, N were determined by TF-Flash-1101 EA, The metals contents of metal chelates were determined volumetrically by Vogel's method 29.To a 100 mg chelate sample, each 1 mL of HCl, H 2 SO 4 and HClO 4 were added and then 1 g of NaClO 4 was added.The mixture was evaporated to dryness and the resulting salt was dissolved in double distilled water and diluted to the mark.From this solution the metal content was determined by titration with standard EDTA solution.Infrared spectra of the synthesized compounds were recorded on Nicolet 760 FT-IR spectrometers.NMR spectrum of secnidazole was recorded on 400 MHz NMR spectrophotometer.Magnetic susceptibility measurement of the synthesized complexes was carried out on Gouy balance at room temperature.The electronic spectra of complexes in solid were recorded at room temperature.MgO was used as reference.Antimicrobial activity of all the samples was monitored against various gram positive and gram negative organism, following the method reported in the literature 30,31.

Elemental analysis
The obtained C, H, N contents of 1-(H)-Secnidazole and its heterochelates are in good agreement with the calculated one as shown in Table 1.

IR analysis
The important infrared spectral bands and their tentative assignments for the synthesized ligands 1-(H)-secnidazole and its complexes were recorded as KBr disks and the data of complexes and ligand are presented in Table 2.
The IR spectrum of comprises the important bands due to 8-quinolinol.The bands were observed at 1635, 1575, 1472 and 755 cm -1 .The broad band in ligand and all the complexes at 3800-2700 cm -1 is due to the presence of -OH group.The band at 1700 cm -1 is due to -CO-group.The band at 1670 cm -1 might be due to carbamide group.In this band the inflections are observed at 2950, 2920 and 2850 cm -1 .While the latter two might be attributed to asymmetric and symmetric vibration of -CH 2 group of CMQ.
The infrared spectra of all the complexes are identical and suggest the formation of the entire metalocyclic compound by the absence of band characteristic of free -OH group of parent 1-(H)-secnidazole.The other bands are almost at their respectable positions as appeared in the spectrum of parent 1-(H)-secnidazole ligand.
However, in the far-IR region, two new bands in the range of 444-472 and 410-430 cm −1 in the all the complexes are assigned the binding of metal with oxygen and nitrogen atom of CMQ respectively.

H NMR analysis
The 1 H NMR spectrum of 1-(H)-secnidazole is carried out in DMSO-d 6 using as solvent indicates that singlet at 1.1 δ ppm due to the aliphatic -CH 3 group protons, where the singlet at 2.5 δ ppm due to the aromatic -CH 3 group protons, two peaks at 3.7-3.

Magnetic measurements
Magnetic moments of heterochelates are given in Table 2.The diffuse electronic spectrum of Cu 2+ chelates shows two broad bands around 13000 and 23000 cm -1 .The first band may be due to a 2 B 1g → 1 A 1g transition, while the second band may be due to charge transfer.The first band shows structures suggesting a distorted octahedral structure for the Cu 2+ metal chelates 32,33 .The higher value of the magnetic moment of the Cu 2+ chelate supports the same.The Co 2+ metal chelate gives rise to two absorption bands at 23800 and 19040 cm -1 , which can be assigned 4 T 1g → 2 T 2g , 4 T 1g → 4 T 1g (P) transitions, respectively.These absorption bands and the µ eff value indicate an octahedral configuration of the Co 2+ metal chelate 34,35 .The spectrum of Mn 2+ polymeric chelate comprised two bands at 19019 cm -1 and 23301 cm -1 .The latter does not have a very long tail.These bands may be assigned to 6 A 1g → 4 T 2g (G) and 6 A 1g → 4 A 2g (G) transitions, respectively.The high intensity of the bands suggests that they may have some charge transfer character.The magnetic moment is found to be lower than normal range.In the absence of low temperature measurement of magnetic moment it is difficult to attach any significance to this.As the spectrum of the metal chelate of Ni 2+ show two Sistine bands at 11961-11490 and 17701-17400 cm -1 are assigned as 3 A 2g (F)→ 3 T 1g (F) and 3 A 2g (F)→ 3 T 1g (F) transition, respectively suggested the octahedral environment for Ni 2+ ion.The observed µ eff values in the range 3.01-3.2B.M are consistent with the above moiety [36][37] .

Antimicrobial screening
To assess the biological potential of the ligands and their macrocyclic complexes, laboratory experiments have been conducted.The following techniques have been used for the antimicrobial activities of these compounds.In this technique sterilized hot nutrient agar medium and 5 mm diameter paper discs of Whatman were used.The agar medium was poured into the petri plates.After solidifications, the petri plates were stored in inverted position so that there was condensation of water in the upper lid.Solutions of test compounds in DMSO in 500 and 1000 ppm concentrations were prepared in which discs were dipped in solution of the test sample placed on seeded plates.The petri plates having these discs on the seeded agar should first be placed at low temperature for two or four hours to allow for the diffusion of chemicals before being incubated at suitable optimum temperature 28 ± 2 o C for 24-30 h.After the expiry of their incubation period, the zone of inhibition associated with the treated disc was measured in mm.The compounds were tested against Pseudomonas aeruginosa, Escherichia coli gram positive and Serratia marcescens, Bacillus substilis gram negative organism.
The examination of antimicrobial activity of 1-(H)-secnidazole ligand and its all heterochelates (Table 3) reveals that the ligand is moderately more or less active against various organisms, while all the heterochelates are more active than ligand.Among all the heterochelates the Cu 2+ chelate is more active against organisms used.

Table 2 .
Spectral features and magnetic moment of MIPQ ligand and it's heterochelates

Table 3 .
Antimicrobial activity of MIPQ lidand and its heterochelates